反应详情

温度

0 °C

To a suspension of 6-cyano-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester (5.7 g, 15.8 mmol) in methanol (130 mL) was added cobalt (II) chloride (7.5 g, 31.6 mmol). The reaction mixture was stirred for 10 minutes, then cooled to 0° C. and sodium borohydride (6.0 g, 158 mmol) was added in small portions over 30 minutes. The reaction mixture was stirred at 0° C. for 15 minutes and then at room temperature for 1 hour. The reaction was quenched by addition of concentrated hydrochloric acid (20 mL) and the mixture stirred for 15 minutes. The reaction mixture was filtered to remove a white solid, which was washed with dichloromethane, and the filtrate was concentrated under reduced pressure. The resultant residue was dissolved in ethyl acetate and washed with a saturated solution of sodium bicarbonate, followed by water then brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a brown solid (2.0 g, 34%). LCMS (method B): RT=2.77 min, [M+H]+=366.

1. stirringThe reaction mixture was stirred at 0° C. for 15 minutes
2. waitat room temperature for 1 hour
3. customThe reaction was quenched by addition of concentrated hydrochloric acid (20 mL)
4. stirringthe mixture stirred for 15 minutes
5. filtrationThe reaction mixture was filtered
6. customto remove a white solid, which
7. washwas washed with dichloromethane
8. concentrationthe filtrate was concentrated under reduced pressure
9. dissolutionThe resultant residue was dissolved in ethyl acetate
10. washwashed with a saturated solution of sodium bicarbonate
11. customThe organic phase was isolated
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo